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CIMIZT 150 MICROGRAM/30 MICROGRAM TABLETS

Active substance(s): DESOGESTREL / ETHINYLESTRADIOL / DESOGESTREL / ETHINYLESTRADIOL / DESOGESTREL / ETHINYLESTRADIOL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Cimizt 150 microgram/30 microgram Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 150 micrograms desogestrel and 30 micrograms ethinylestradiol.
Excipients: 1 uncoated tablet contains 58 mg of lactose anhydrous
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Tablet
Each tablet is round, white to off-white, 5.00 mm, uncoated, biconvex, debossed with
‘142’ on one side and other side plain.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Oral contraception
The decision to prescribe Cimizt should take into consideration the individual
woman’s current risk factors, particularly those for venous thromboembolism (VTE),
and how the risk of VTE with Cimizt compares with other CHCs (see sections 4.3
and 4.4).

4.2

Posology and method of administration
Route of administration: Oral use

How to take Cimizt Tablets

The tablets must be taken every day at about the same time, if necessary with a little
liquid, in the order shown on the blister pack. One tablet is to be taken daily for 21
consecutive days. Each subsequent pack is started after a 7-day tablet-free interval;
during which time a withdrawal bleeding usually occurs. This usually starts on day
2-3 after the last tablet and may not have finished before the next pack is started.
How to start Cimizt Tablets
No preceding hormonal contraceptive use (in the past month)
Tablet-taking has to start on day 1 of the woman’s natural cycle (i.e. the first day of
her menstrual bleeding). Tablet intake is also allowed to start on day 2-5, but during
the first cycle concurrent use of a barrier method for the first 7 days of tablet intake is
advisable.


Changing from a combined hormonal contraceptive (combined oral
contraceptive (COC), vaginal ring or transdermal patch)

The woman should start taking Cimizt Tablets preferably on the day after the last
active tablet (the last tablet containing the active substances) of her previous COC,
but at the latest on the day following the usual tablet-free or placebo tablet interval of
her previous COC. In case a vaginal ring or a transdermal patch has been used, the
woman should start using preferably on the day of removal, but at the latest when the
next application would have been due.


Changing from a progestogen-only-method (progestogen-only-pill, injection,
implant) or from a progestogen-releasing intrauterine system (IUS)

The woman may switch any day from the progestogen-only pills (from an implant or
the IUS on the day of its removal; from an injectable when the next injection would
be due) but should in all of these cases be advised to additionally use a barrier method
for the first 7 days of tablet-taking.


Following first-trimester abortion

The woman may start immediately. When doing so, she need not take additional
contraceptive measures.


Following delivery or second-trimester abortion

The woman should be advised to start at day 21 to 28 after delivery or secondtrimester abortion. When starting later, the woman should be advised to additionally
use a barrier method for the first 7 days. However if intercourse has already occurred,
pregnancy should be excluded before the actual start of COC use or the woman has to
wait for her first menstrual period.

For breastfeeding women - see section 4.6.

Management of missed tablets
If the user is less than 12 hours late in taking any tablet, contraceptive protection is
not reduced.
The woman should take the tablet as soon as she remembers, and should take further
tablets at usual time.
If she is more than 12 hours late in taking any tablet, contraceptive protection may
be reduced. The management of missed tablets can be guided by the following two
basic rules:
1. tablet-taking must never be discontinued for longer than 7 days
2. 7 days of uninterrupted tablet-taking are required to attain adequate suppression of
the hypothalamus-pituitary-ovarian-axis.
Accordingly the following advice can be given in daily practice:


Week 1

The user should take the last missed tablet as soon as she remembers, even if this
means taking two tablets at the same time. She then continues to take tablets at her
usual time. In addition, a barrier method such as a condom should be used for the next
7 days. If intercourse took place in the preceding 7 days, the possibility of a
pregnancy should be considered. The more tablets are missed and the closer they are
to the regular tablet-free interval, the higher the risk of a pregnancy.


Week 2

The user should take the last missed tablet as soon as she remembers, even if this
means taking two tablets at the same time. She then continues to take tablets at her
usual time. Provided that the woman has taken her tablets correctly in the 7 days
preceding the first missed tablet, there is no need to use extra contraceptive
precautions. However, if she has missed more than 1 tablet, the woman should be
advised to use extra precautions for 7 days.


Week 3

The risk of reduced reliability is imminent because of the forthcoming 7-day tabletfree interval. However, by adjusting the tablet-intake schedule, reduced contraceptive
protection can still be prevented. By adhering to either of the following two options,
there is therefore no need to use extra contraceptive precautions, provided that in the
7 days preceding the first missed tablet the woman has taken all tablets correctly. If
this is not the case, she should follow the first of these two options and use extra
precautions for the next 7 days as well.
1. The user should take the last missed tablet as soon as she remembers, even if this
means taking two tablets at the same time. She then continues to take tablets at her
usual time. The next blister pack must be started as soon as the current blister pack is
finished, i.e., no gap should be left between packs. The user is unlikely to have a

withdrawal bleed until the end of the second pack, but she may experience spotting or
breakthrough bleeding on tablet-taking days.
2. The woman may also be advised to discontinue tablet-taking from the current
blister pack. She should then have a tablet-free interval of up to 7 days, including the
days she missed tablets, and subsequently continue with the next blister pack.
If the woman missed tablets and subsequently has no withdrawal bleed in the first
normal tablet-free interval, the possibility of a pregnancy should be considered.

Advice in case of gastro-intestinal disturbances
In case of severe gastro-intestinal disturbances (e.g., vomiting or diarrhoea),
absorption may not be complete and additional contraceptive measures should be
taken. If vomiting occurs within 3-4 hours after tablet-taking, a new (replacement)
tablet should be taken as soon as possible. The new tablet should be taken within 12
hours of the usual time of tablet-taking if possible. If more than 12 hours elapse, the
advice concerning missed tablets, under section “Management of missed tablets”, is
applicable. If the woman does not want to change her normal tablet-taking schedule,
she has to take the extra tablet(s) from another blister pack.
How to postpone a withdrawal bleed
To delay a period the woman should continue with another blister pack of Cimizt
Tablets without a tablet-free interval. The extension can be carried on for as long as
wished until the end of the second pack. During the extension the woman may
experience breakthrough-bleeding or spotting. Regular intake of Cimizt Tablets is
then resumed after the usual 7-day tablet-free interval.
To shift her periods to another day of the week than the woman is used to with her
current scheme, she can be advised to shorten her forthcoming tablet-free interval by
as many days as she likes. The shorter the interval, the higher the risk that she does
not have a withdrawal bleed and will experience breakthrough-bleeding and spotting
during the subsequent pack (just as when delaying a period).

4.3

Contraindications
Combined oral contraceptives (COCs) should not be used in the presence of any of
the conditions listed below. Should any of the conditions appear for the first during
COC use, the product should be stopped immediately
-

Pancreatitis or a history thereof if associated with severe
hypertriglyceridemia
Presence or history of severe hepatic disease as long as liver function values
have not returned to normal.
Presence or history of liver tumours (benign or malignant).
Known or suspected sex steroid-influenced malignancies (e.g. of the genital
organs or the breasts)
Undiagnosed vaginal bleeding.
History of migraine with focal neurological symptoms

-

Hypersensitivity to the active substances or to any of the excipients of Cimizt
Tablets.

Cimizt is contraindicated for concomitant use with the medicinal products containing
ombitasvir/paritaprevir/ritonavir and dasabuvir (see sections 4.4 and section 4.5).


Presence or risk of venous thromboembolism (VTE)

o Venous thromboembolism – current VTE (on anticoagulants) or history of
(e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE])
o Known hereditary or acquired predisposition for venous
thromboembolism, such as APC-resistance, (including Factor V Leiden),
antithrombin-III-deficiency, protein C deficiency, protein S deficiency
o Major surgery with prolonged immobilisation (see section 4.4)
o A high risk of venous thromboembolism due to the presence of multiple
risk factors (see section 4.4)


4.4

Presence or risk of arterial thromboembolism (ATE)
o Arterial thromboembolism – current arterial thromboembolism, history of
arterial thromboembolism (e.g. myocardial infarction) or prodromal
condition (e.g. angina pectoris)
o Cerebrovascular disease – current stroke, history of stroke or prodromal
condition (e.g. transient ischaemic attack, TIA)
o Known hereditary or acquired predisposition for arterial
thromboembolism, such as hyperhomocysteinaemia and antiphospholipidantibodies (anticardiolipin-antibodies, lupus anticoagulant).
o History of migraine with focal neurological symptoms.
o A high risk of arterial thromboembolism due to multiple risk factors (see
section 4.4) or to the presence of one serious risk factor such as:
• diabetes mellitus with vascular symptoms
• severe hypertension
• severe dyslipoproteinaemia

Special warnings and precautions for use

Warnings
If any of the conditions or risk factors mentioned below is present, the suitability of
Cimizt should be discussed with the woman.
In the event of aggravation, or first appearance of any of these conditions or risk
factors, the woman should be advised to contact her doctor to determine whether the
use of Cimizt should be discontinued.
Risk of venous thromboembolism (VTE)
Circulatory disorders
The use of any combined oral contraceptive carries an increased risk of venous
thromboembolism (VTE) compared with no use. The excess risk of VTE is highest
during the first year a woman ever uses a combined oral contraceptive. Products that
contain levonorgestrel, norgestimate or norethisterone are associated with the lowest
risk of VTE. Other products such as Cimizt may have up to twice this level of risk.
The decision to use any product other than one with the lowest VTE risk should be
taken only after a discussion with the woman to ensure she understands the risk of
VTE with Cimizt, how her current risk factors influence this risk, and that her VTE
risk is highest in the first ever year of use. There is also some evidence that the risk is
increased when a CHC is re-started after a break in use of 4 weeks or more.
In women who do not use a CHC and are not pregnant about 2 out of 10,000 will
develop a VTE over the period of one year. However, in any individual woman the
risk may be far higher, depending on her underlying risk factors (see below).
It is estimated1that out of 10,000 women who use a CHC containing desogestrel
between 9 and 12 women will develop a VTE in one year; this compares with about
62in women who use a levonorgestrel-containing CHC.
In both cases, the number of VTEs per year is fewer than the number expected during
pregnancy or in the postpartum period.
VTE may be fatal in 1-2% of cases.

Number of VTE events per 10,000 women in one year

1

These incidences were estimated from the totality of the epidemiological study data, using relative
risks for the different products compared with levonorgestrel-containing CHCs.
2
Mid-point of range of 5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel
versus non-use of approximately 2.3 to 3.6

Number of
VTE
14 events

12

10

8

6

4

2

0

Non-CHCuser (2 events)

Levonorgestrel-containing CHC(5-7
events)

Desogestrel-containing CHC(9-12
events)

Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels,
e.g. hepatic, mesenteric, renal or retinal veins and arteries.

Risk factors for VTE
The risk for venous thromboembolic complications in CHC users may increase
substantially in a woman with additional risk factors, particularly if there are multiple
risk factors (see table).
Cimizt is contraindicated if a woman has multiple risk factors that put her at high risk
of venous thrombosis (see section 4.3). If a woman has more than one risk factor, it is
possible that the increase in risk is greater than the sum of the individual factors – in
this case her total risk of VTE should be considered. If the balance of benefits and
risks is considered to be negative a CHC should not be prescribed (see section 4.3).
Table: Risk factors for VTE
Risk factor

Comment

Obesity (body mass index over 30
kg/m²)

Risk increases substantially as BMI rises.

Prolonged immobilisation, major
surgery, any surgery to the legs or
pelvis, neurosurgery, or major
trauma

In these situations it is advisable to discontinue
use of the patch/pill/ring (in the case of elective
surgery at least four weeks in advance) and not
resume until two weeks after complete
remobilisation. Another method of contraception
should be used to avoid unintentional pregnancy.

Particularly important to consider if other risk
factors also present.

Antithrombotic treatment should be considered
if [invented name] has not been discontinued in
advance.

Note: temporary immobilisation
including air travel >4 hours can
also be a risk factor for VTE,
particularly in women with other
risk factors
Positive family history (venous
If a hereditary predisposition is suspected, the
thromboembolism ever in a sibling woman should be referred to a specialist for
or parent especially at a relatively advice before deciding about any CHC use
early age e.g. before 50).
Other medical conditions
associated with VTE

Cancer, systemic lupus erythematosus,
haemolytic uraemic syndrome, chronic
inflammatory bowel disease (Crohn’s disease or
ulcerative colitis) and sickle cell disease

Increasing age

Particularly above 35 years

There is no consensus about the possible role of varicose veins and superficial
thrombophlebitis in the onset or progression of venous thrombosis.
The increased risk of thromboembolism in pregnancy, and particularly the 6 week
period of the puerperium, must be considered (for information on “Pregnancy and
lactation” see section 4.6).
Symptoms of VTE (deep vein thrombosis and pulmonary embolism)
In the event of symptoms women should be advised to seek urgent medical attention
and to inform the healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include:
- unilateral swelling of the leg and/or foot or along a vein in the leg;
- pain or tenderness in the leg which may be felt only when standing or
walking,
- increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include:
- sudden onset of unexplained shortness of breath or rapid breathing;
- sudden coughing which may be associated with haemoptysis;
- sharp chest pain;
- severe light headedness or dizziness;
- rapid or irregular heartbeat.
Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific and
might be misinterpreted as more common or less severe events (e.g. respiratory tract
infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue
discoloration of an extremity.

If the occlusion occurs in the eye symptoms can range from painless blurring of vision
which can progress to loss of vision. Sometimes loss of vision can occur almost
immediately.
Risk of arterial thromboembolism (ATE)
Epidemiological studies have associated the use of CHCs with an increased risk for
arterial thromboembolism (myocardial infarction) or for cerebrovascular accident
(e.g. transient ischaemic attack, stroke). Arterial thromboembolic events may be fatal.
Risk factors for ATE
The risk of arterial thromboembolic complications or of a cerebrovascular accident in
CHC users increases in women with risk factors (see table). Cimizt is contraindicated
if a woman has one serious or multiple risk factors for ATE that puts her at high risk
of arterial thrombosis (see section 4.3). If a woman has more than one risk factor, it is
possible that the increase in risk is greaterthan the sum of the individual factors - in
this case her total risk should be considered. If the balance of benefits and risks is
considered to be negative a CHC should not be prescribed (see section 4.3).

Table: Risk factors for ATE
Risk factor

Comment

Increasing age

Particularly above 35 years

Smoking

Women should be advised not to smoke if they
wish to use a CHC. Women over 35 who
continue to smoke should be strongly advised to
use a different method of contraception.

Hypertension
Obesity (body mass index over 30
kg/m2)

Risk increases substantially as BMI increases.
Particularly important in women with additional
risk factors

Positive family history (arterial
If a hereditary predisposition is suspected, the
thromboembolism ever in a
woman should be referred to a specialist for
sibling or parent especially at
advice before deciding about any CHC use
relatively early age e.g. below 50).
Migraine

An increase in frequency or severity of migraine
during CHC use (which may be prodromal of a
cerebrovascular event) may be a reason for
immediate discontinuation

Other medical conditions
associated with adverse vascular
events

Diabetes mellitus, hyperhomocysteinaemia,
valvular heart disease and atrial fibrillation,
dyslipoproteinaemia and systemic lupus
erythematosus.

Symptoms of ATE
In the event of symptoms women should be advised to seek urgent medical attention
and to inform the healthcare professional that she is taking a CHC.
Symptoms of a cerebrovascular accident can include:
- sudden numbness or weakness of the face, arm or leg, especially on one side
of the body; motor disturbances;
- sudden trouble walking, vertigo, dizziness, loss of balance or coordination;
- sudden confusion, trouble speaking or understanding; slurred speech or
aphasia;
- sudden trouble seeing in one or both eyes; diplopia
- sudden, severe or prolonged headache with no known cause
- loss of consciousness or fainting/collapse with or without seizure.
-acute abdomen
Temporary symptoms suggest the event is a transient ischaemic attack (TIA).
Symptoms of myocardial infarction (MI) can include:
- pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in
the chest, arm, or below the breastbone;
- discomfort radiating to the back, jaw, throat, arm, stomach;
- feeling of being full, having indigestion or choking;
- sweating, nausea, vomiting or dizziness;
- extreme weakness, anxiety, or shortness of breath;
- rapid or irregular heartbeats.

The presence of one serious risk factor or multiple risk factors for venous or arterial
disease, respectively, can also constitute a contra-indication. The possibility of
anticoagulant therapy should also be taken into account. COC users should be
specifically pointed out to contact their physician in case of possible symptoms of
thrombosis. In case of suspected or confirmed thrombosis, COC use should be
discontinued. Adequate alternative contraception should be initiated because of the
teratogenicity of anticoagulant therapy (coumarins).
The increased risk of thromboembolism in the puerperium must be considered (for
information on “Pregnancy and lactation” – see section 4.6).
An increase in frequency or severity of migraine during use of COCs (which may be
prodromal of a cerebrovascular event) may be a reason for immediate discontinuation
of the COC.

Tumours

An increased risk of cervical cancer in long-term users of COCs (> 5 years) has been
reported in some epidemiological studies, but there continues to be controversy about
the extent to which this finding is attributable to the confounding effects of sexual
behaviour and other factors such as human papilloma virus (HPV).
A meta-analysis from 54 epidemiological studies reported that there is a slightly
increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who
are currently using COCs. The excess risk gradually disappears during the course of
the 10 years after cessation of COC use. Because breast cancer is rare in women
under 40 years of age, the excess number of breast cancer diagnoses in current and
recent users of COCs is small in relation to the overall risk of breast cancer. These
studies do not provide evidence for causation. The observed pattern of increased risk
may be due to an earlier diagnosis of breast cancer in users of COCs, the biological
effects of COCs or a combination of both. The breast cancers diagnosed in ever-users
tend to be less advanced clinically than the cancers diagnosed in never-users.
In rare cases, benign liver tumours, and even more rarely malignant liver tumours
have been reported in users of COCs. In isolated cases, these tumours have led to lifethreatening intra-abdominal haemorrhages. A hepatic tumour should be considered in
the differential diagnosis when severe upper abdominal pain, liver enlargement or
signs of intra-abdominal haemorrhage occur in women taking COCs.
With the use of the higher-dosed COCs (50 µg ethinylestradiol) the risk of
endometrial and ovarian cancer is reduced. Whether this also applies to lower-dosed
COCs remains to be confirmed.

ALT elevations
During clinical trials with patients treated for hepatitis C virus infections (HCV) with
the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir
with or without ribavirin, transaminase (ALT) elevations higher than 5 times the
upper limit of normal (ULN) occurred significantly more frequent in women using
ethinylestradiol-containing medications such as combined hormonal contraceptives
(CHCs) (see sections 4.3 and 4.5).

Other conditions
Women with hypertriglyceridaemia or a family history thereof may be at increased
risk of pancreatitis when using COCs.
Although small increases in blood pressure have been reported in many women
taking COCs, clinically relevant increases are rare. Only in these rare cases an
immediate discontinuation of COC use is justified. A systematic relationship between
COC use and clinical hypertension has not been established. If, during the use of a
COC in preexisting hypertension, constantly elevated blood pressure values or a
significant increase in blood pressure do not respond adequately to antihypertensive
treatment, the COC must be withdrawn. Where considered appropriate, COC use may
be resumed if normotensive values can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both
pregnancy and COC use, but the evidence of an association with COC use is
inconclusive: Jaundice and/or pruritus related to cholestasis; gallstones; porphyria;

systemic lupus erythematosus; haemolytic uremic syndrome; Sydenham’s chorea;
herpes gestationis; otosclerosis-related hearing loss.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate
symptoms of angioedema.
Acute or chronic disturbances of liver function may necessitate discontinuation of
COC use until markers of liver function return to normal. Recurrence of cholestatic
jaundice and/or cholestasis-related pruritus which previously occurred during
pregnancy or during previous use of sex steroids necessitates the discontinuation of
COCs.
Although COCs may have an effect on peripheral insulin resistance and glucose
tolerance, there is no evidence for a need to alter the therapeutic regime in diabetics
using low-dose COCs (containing <0.05 mg ethinylestradiol). However, diabetic
women should be carefully observed, particularly in the early stage of COC use.
Worsening of endogenous depression, of epilepsy, of Crohn’s disease and of
ulcerative colitis has been reported during COC use.
Chloasma may occasionally occur, especially in women with a medical history of
chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to
sunlight or ultra-violet radiation whilst taking COCs.
Cimizt Tablets contains lactose. Patients with rare hereditary problems of galactose
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should
not take this medicinal product.
Medical examination/consultation

Prior to the initiation or reinstitution of Cimizt Tablets a complete medical
history (including family history) should be taken and pregnancy must be
ruled out. Blood pressure should be measured and a physical examination
should be performed, guided by the contra-indications (section 4.3) and
warnings (section 4.4). It is important to draw a woman’s attention to the
information on venous and arterial thrombosis, including the risk of Cimizt
compared with other CHCs, the symptoms of VTE and ATE, the known risk
factors and what to do in the event of a suspected thrombosis.
The woman should also be instructed to carefully read the user leaflet and to adhere to
the advice given. The frequency and nature of examinations should be based on
established practice guidelines and be adapted to the individual woman.
Women should be advised that oral contraceptives do not protect against HIV
infections (AIDS) or other sexually transmitted diseases.

Reduced efficacy
The efficacy of COCs may be reduced in the event of e.g. missed tablets (section
4.2.), gastro-intestinal disturbances (section 4.2.) or concomitant medication (section
4.5.).
Reduced cycle control
With all COCs, irregular bleeding (spotting and breakthrough bleeding) may occur,
especially during the first months of use. Therefore, the evaluation of any irregular
bleeding is only meaningful after an adaptation interval of about 3 cycles.
If bleeding irregularities persist or occur after previously regular cycles, then nonhormonal causes should be considered and adequate diagnostic measures are
indicated to exclude malignancy or pregnancy. These may include curettage.
In some women withdrawal bleeding may not occur during the tablet-free interval. If
the COC has been taken according to the directions described in section 4.2, it is
unlikely that the woman is pregnant. However, if the COC has not been taken
according to these directions prior to the first missed withdrawal bleed or if two
withdrawal bleeds are missed, pregnancy must be ruled out before COC use is
continued.

4.5

Interaction with other medicinal products and other forms of interaction
Note: The prescribing information of concomitant medications should be consulted to
identify potential interactions.

Influence of other medical products on Cimizt Tablets
Interactions between oral contraceptives and other medicinal products may lead to
breakthrough bleeding and/or contraceptive failure. The following interactions have
been reported in the literature.
Hepatic metabolism
Interactions can occur with drugs that induce hepatic enzymes which can result in
increased clearance of sex hormones (e.g. phenytoin, barbiturates, primidone,
carbamazepine, rifampicin, bosentan and HIV-medication (e.g. ritonavir, nevirapine)
and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products
containing the herbal remedy St. John's Wort (Hypericum perforatum). Maximal

enzyme induction is generally seen in about 10 days but may then be sustained for at
least 4 weeks after the cessation of drug therapy.
Interference with Enterohepatic Circulation
Contraceptive failures have also been reported with antibiotics, such as penicillins
and tetracyclines. The mechanism of this effect has not been elucidated.
Management
Women on short-term treatment with any of the above-mentioned classes of
medicinal products or individual active substances (hepatic enzyme-inducing
medicine) besides rifampicin should temporarily use a barrier method in addition to
the COC, i.e. during the time of concomitant medicinal product administration and
for 7 days after their discontinuation.
For women on rifampicin a barrier method should be used in addition to the COC
during the time of rifampicin administration and for 28 days after its discontinuation.
In women on long-term treatment with hepatic enzyme-inducing active substances,
another reliable, non-hormonal, method of contraception is recommended.
Women on treatment with antibiotics (besides rifampicin, see above) should use the
barrier method until 7 days after discontinuation.
If concomitant medicinal product administration runs beyond the end of the tablets in
the COC blister pack, the next COC pack should be started without the usual tabletfree interval.

Influence of Cimizt Tablets on other medicinal products
Oral contraceptives may affect the metabolism of certain other active substances.
Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin)
or decrease (e.g. lamotrigine).
Laboratory analyses
The use of contraceptive steroids may influence the results of certain laboratory tests,
including biochemical parameters of liver, thyroid, adrenal and renal function; plasma
levels of (carrier) proteins, e.g. corticosteroid-binding globulin and lipid/lipoprotein
fractions, parameters of carbohydrate metabolism and parameters of coagulation and
fibrinolysis. Changes generally remain within the normal laboratory range.
Pharmacodynamic interactions
Concomitant
use
with
the
medicinal
products
containing
ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin may increase
the risk of ALT elevations (see sections 4.3 and 4.4).
Therefore, Cimizt users must switch to an alternative method of contraception

(e.g., progestagen-only contraception or non-hormonal methods) prior to starting
therapy with this combination drug regimen. Cimizt can be restarted 2 weeks
following completion of treatment with this combination drug regimen.

4.6

Fertility, pregnancy and lactation
Cimizt Tablets is not indicated in pregnancy.
The increased risk of VTE during the postpartum period should be considered when
re-starting Cimizt (see section 4.2 and 4.4).
If pregnancy occurs during the use of Cimizt Tablets the preparation should be
withdrawn immediately. Extensive epidemiological studies have revealed neither an
increased risk of birth defects in children born to women who used COCs prior to
pregnancy, nor a teratogenic effect when COCs were taken inadvertently during
pregnancy.
Lactation may be influenced by COCs as they may reduce the quantity and change
the composition of breast milk. Therefore, the use of COCs should generally not be
recommended until the breast-feeding mother has completely weaned her child. Small
amounts of the contraceptive steroids and/or their metabolites may be excreted with
the milk during COC use. These amounts may affect the child.

4.7

Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been
performed. No effects on ability to drive and use machines have been observed in
users of COCs.

4.8

Undesirable effects
For serious adverse experiences in users of COCs see section 4.4.
There is an increased risk of arterial and venous thrombotic and thrombo-embolic
events, including myocardial infarction, stroke, transient ischemic attacks, venous
thrombosis and pulmonary embolism has been observed in women using a COC.
For information on differences in risk between COCs, see Section 4.4.

Organ systems

Very common

Common

Rare

>1/10

/Uncommon

less than 1/1000

(more than 1/1,000
but less than 1/10)

Infections and

Vaginal

infestations

candidiasis

Immune system

Hypersensitivity

disorders
Metabolism and

Fluid retention

nutrition disorders
Psychiatric

Libido decreased

disorders

Depressed mood

Libido increased

Mood altered
Nervous system

Headache

disorders

Dizziness
Nervousness

Eye disorders

Contact lens
intolerance

Ear and labyrinth

Otosclerosis

disorders
Vascular disorders

Migraine
Hypertension

Thromboembolism
(venous and arterial)

Gastrointestinal

Nausea

disorders

Vomiting

Skin and

Acne

Erythema

subcutaneous

Rash

nodosum

tissue disorders

Urticaria

Erythema
multiforme
Pruritus
Alopecia

Reproductive

Irregular

Amenorrhea

Vaginal

system and breast

bleeding

Breast tenderness

discharge

Breast pain

Breast discharge

disorders

Breast hypertrophy
Metrorrhagia
General disorders

Weight

and administration

increase

site conditions

The following serious adverse events have been reported in women using COCs and
are discussed in section 4.4:

-

Venous thromboembolic disorders;

-

Arterial thromboembolic disorders;

-

Hypertension;

-

Liver tumours;

-

Occurrence or deterioration of conditions for which an association with OC
use is not conclusive: Crohn's disease, ulcerative colitis, epilepsy, migraine,
endometriosis, uterine myoma, porphyria, systemic lupus erythematosus,
herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome,
cholestatic jaundice;

-

Chloasma;

-

Acute or chronic disturbances of liver function may necessitate the
discontinuation of COC use until markers of liver function return to normal.

-

In women with hereditary angioedema exogenous estrogens may induce or
exacerbate symptoms of angioedema.

The frequency of diagnosis of breast cancer is very slightly increased among OC
users. As breast cancer is rare in women under 40 years of age the excess number is
small in relation to the overall risk of breast cancer. Causation with COC use is
unknown. For further information, see sections 4.3 and 4.4.

4.9

Overdose
There has not been any experience of overdose with Cimizt Tablets. On the basis of
general experience with combined oral contraceptives, symptoms that may possibly
occur in this case are: nausea, vomiting and, in young girls, slight vaginal bleeding.
There are no antidotes and further treatment should be symptomatic.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Progestogens and estrogens, fixed combinations
ATC code: G 03 AA 09
The contraceptive action of COCs is based on interaction of different factors, out of
which the most important is the inhibition of ovulation and changes in the cervical
secretion. Besides protection against pregnancy, COCs have several positive
properties which, next to the negative properties (see Warnings, Undesirable effects),
can be useful in deciding on the method of birth control. The cycle is more regular
and the menstruation is often less painful and bleeding is lighter. The latter may result

in a decrease in the occurrence of iron deficiency. In the largest multicenter trial
(n=23 258 cycles), the uncorrected Pearl Index is estimated at 0.1 (95% confidence
interval 0.0-0.3). Furthermore, 4.5% of the women reported absence of withdrawal
bleeding and 9.2% reported occurrence of irregular bleeding after 6 treatment cycles.
Cimizt Tablets is a COC with ethinylestradiol and the progestogen desogestrel.
Ethinylestradiol is a well known synthetic estrogen.
Desogestrel is a synthetic progestogen. After oral administration it has a strong
ovulation-inhibiting activity.
With the use of the higher-dosed COCs (50μg ethinylestradiol) the risk of
endometrial and ovarian cancer is reduced. Whether this also applies to lower-dosed
COCs remains to be confirmed.

5.2

Pharmacokinetic properties
Desogestrel
Absorption
After oral administration of desogestrel 150 micrograms and ethinylestradiol 30
micrograms tablets, desogestrel is rapidly absorbed and converted into 3-ketodesogestrel. Peak plasma levels are reached after 1.5 hours. The absolute
bioavailability of 3-keto-desogestrel is 62-81%.
Distribution
3-keto-desogestrel is 95.5-99% bound to the plasma proteins, mainly albumin and
SHBG. The ethinyl-oestradiol-induced increase in SHBG influences both the amount
of bindings and distribution of 3-keto-deosgestrel in the plasma proteins. As a
consequence the concentration of 3-keto-desogestrel rises slowly during treatment
until steady state is reached within 3-13 days.
Metabolism
The phase-I metabolism of desogestrel includes cytochrome P-450 catalysed
hydroxylation and subsequent dehydrogenation at C3. The active metabolite of 3keto-desogestrel is further reduced, the degradation products are conjugated to
sulphate and glucuronides. Animal studies indicate that the enterohepatic circulation
has no relevance for the gestagenic activity of desogestrel.
Elimination
3-keto-desogestrel is eliminated with a mean half-life of approx. 31 hours (24-38
hours), plasma clearance varies from 5.0-9.5 l/hour. Desogestrel and its metabolites
are eliminated via the urine and in the faeces, either as free steroids or conjugates.
Ratio for elimination in urine or faeces is 1.5:1.

Steady-State Conditions
In steady-state conditions the serum level of 3-keto-desogestrel is elevated by two- to
threefold.

Ethinylestradiol
Absorption
Ethinyl estradiol is rapidly absorbed and peak plasma levels are reached after 1.5
hours. As a consequence of presystemic conjugation and first-pass metabolism the
absolute bioavailability is 60%. The area under the curve and Cmax may be expected
to rise slightly over time.
Distribution
Ethinyl estradiol is 98.8% bound to the plasma proteins, almost exclusively to
albumin.
Metabolism
Ethinyl estradiol undergoes presystemic conjugation both in the mucosa of the small
intestine and in the liver. Hydrolysis of the direct conjugates of ethinyl estradiol with
the aid of the intestinal flora gives ethinyl estradiol, which can be re-absorbed, and an
enterohepatic circulation is hereby set up. The primary pathway of ethinyl estradiol
metabolism is cytochrome P-450-mediated hydroxylation in which the primary
metabolites are 2-OH-EE and 2-methoxy-EE. 2-OH-EE is further metabolised to
chemically reactive metabolites.
Elimination
Ethinyl estradiol disappears from plasma with a half-life of approx. 29 hours (26-33
hours), plasma clearance varies from 10-30 l/hour. The conjugates of ethinyl estradiol
and its metabolites are excreted via urine and faeces (ratio 1:1).
Steady-state conditions
Steady-state conditions are obtained after 3 to 4 days, when the serum drug level is
approx. 30 to 40% higher than after the administration of a single dose.

5.3

Preclinical safety data
Toxicological studies have not revealed other effects than those, which can be
explained, based on the hormone profile of Cimizt Tablets.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
all-rac-alpha-tocopherol
Potato starch
Povidone (E1201)
Stearic acid (E570)
Silica, colloidal anhydrous (E551)
Lactose, anhydrous

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
2 years

6.4

Special precautions for storage
Do not store above 25°C and store in the original package in order to protect from
moisture and light.

6.5

Nature and contents of container
Clear transparent PVC/PVdC- Aluminium blister of 21 tablets per calender blister
strip available in packs containing 1x21, 3x21 or 6x21 tablets. Each blister is packed
in trilaminated pouch.
Clear transparent PVC/PVdC- Aluminium blister of 21 tablets per calender blister
strip available in packs containing 1x21, 3x21 or 6x21 tablets. Each blister is packed
in trilaminated pouch along with 2g molecular sieve.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements.
Any unused product or waste material should be disposed of in accordance with local
requirements.

7

MARKETING AUTHORISATION HOLDER
Morningside Healthcare Ltd
115 Narborough Road
Leicester
LE3 0PA
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 20117/0231

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
28/05/2012

10

DATE OF REVISION OF THE TEXT
29/08/2017

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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